DESTINY-Breast05 Head-to-Head Phase 3 Trial of ENHERTU® Versus T-DM1 Initiated in Patients with HER2 Positive Early Breast Cancer at High Risk After Neo-adjuvant Therapy

TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ USA I November 02, 2020 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced the initiation of DESTINY-Breast05, a global phase 3, head-to-head trial of ENHERTU® (fam-trastuzumab deruxtecan-nxki) versus ado-trastuzumab emtansine (T-DM1) as adjuvant therapy in patients with HER2 positive early breast cancer with high risk of disease recurrence who have residual invasive disease in the breast or axillary lymph nodes after receiving neo-adjuvant therapy. DESTINY-Breast05 will be conducted in collaboration with the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and the SOLTI Breast Cancer Research Group.

Neo-adjuvant treatment is given before surgery to help shrink the tumor and make it easier to remove. Patients with residual invasive disease in the breast or lymph nodes at surgery following neo-adjuvant treatment are at greater risk for disease recurrence or death than patients who achieve a pathological complete response, meaning there is no detectable disease in the tissue removed during surgery.1 Adjuvant treatment, given after surgery, aims to eradicate any remaining cancer cells in the breast or the rest of the body, to help lower the risk of the cancer returning.

“Despite recent improvements and approvals of new medicines, there remain significant clinical needs for patients with HER2 positive early breast cancer with residual invasive disease after completing neo-adjuvant treatment. We recognize the important opportunity that exists post-surgery to slow disease progression with further adjuvant treatment,” said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. “This research builds on the data from DESTINY-Breast01 which showed durability of response in previously treated HER2 positive metastatic breast cancer. DESTINY-Breast05 will evaluate ENHERTU in patients with early HER2 positive breast cancer, versus T-DM1, the current standard of care, which marks the first time we will evaluate the clinical benefit of ENHERTU in early breast cancer, reflecting our commitment to transforming treatment for even more patients with HER2 targetable disease.”

“NSABP and our academic collaborators are committed to designing and conducting trials that have potential for further improving the way breast cancer is treated by evaluating promising new therapies that may provide patients and physicians with additional treatment options,” said Charles E. Geyer, Jr, MD, chair of the NSABP Foundation Breast Cancer Committee and Deputy Director of the Houston Methodist Cancer Center. “We are excited to collaborate with Daiichi Sankyo and AstraZeneca on this important study, with the goal of comparing the safety and clinical benefit of the two currently available HER2 directed antibody drug conjugates in early stage breast cancer.”

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About DESTINY-Breast05
DESTINY-Breast05 is a phase 3, multicenter, randomized, open-label, active-controlled study of ENHERTU versus T-DM1 in patients with high-risk HER2 positive primary breast cancer who have residual invasive disease in breast or axillary lymph nodes following neo-adjuvant therapy. Patients will be defined as high risk based on inoperable cancer at disease presentation (clinical stages T4, N0-3, M0 or T1-3, N2-3, M0) or operable at presentation (clinical stages T1-3, N0-1, M0) with positive pathological node status (ypN1-3) after neo-adjuvant therapy.

Patients will be randomized in a 1:1 ratio to either the ENHERTU or T-DM1 treatment group. Randomization will be stratified by the following factors:

  • Operative status at disease presentation, prior to neo-adjuvant therapy (operable [clinical stages T1-3, N0-1, M0] versus inoperable [clinical stages T4, N0-3, M0 or T1-3, N2-3, M0])
  • Tumor hormone receptor status (positive versus negative)
  • Post-neo-adjuvant therapy pathologic nodal status (positive [ypN1-3] versus negative [ypN0])
  • HER2 targeted neo-adjuvant therapy approach (single versus dual)

The primary efficacy endpoint is invasive disease-free survival (IDFS) based on investigator assessment. Secondary efficacy endpoints include overall survival and disease-free survival based on disease recurrence per investigator assessment. Safety endpoints include serious adverse events, treatment-emergent adverse events and adverse events of special interest. Health economics and outcomes research endpoints as well as pharmacokinetic and biomarker endpoints will also be measured.

DESTINY-Breast05 will enroll up to 1,600 patients at approximately 400 sites in North America, Europe, and Asia. For more information about the study, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer
In women, breast cancer is the most common cancer and one of the most common causes of cancer mortality worldwide; there were an estimated 2.1 million new cases of female breast cancer diagnosed in 2018.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including gastric, breast and lung cancers. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and poor prognosis in breast cancer.3

About ENHERTU
ENHERTU is a HER2 directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is comprised of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker.

ENHERTU (5.4 mg/kg) is approved in the U.S. under Accelerated Approval and Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who received two or more prior anti-HER2 based regimens based on the DESTINY-Breast01 trial. ENHERTU (6.4 mg/kg) is also approved in Japan for the treatment of patients with HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy based on the DESTINY-Gastric01 trial.

About the ENHERTU Clinical Development Program
A comprehensive development program is underway globally with eight registrational trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

In October 2020, ENHERTU was granted Priority Review from the U.S. Food and Drug Administration (FDA) for the treatment of patients with HER2 positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. In May 2020, ENHERTU received a Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) for gastric cancer, including GEJ adenocarcinoma.

In May 2020, ENHERTU also received a BTD for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy. ENHERTU is not approved in the U.S. in either NSCLC or gastric cancer.

In July 2020, the European Medicines Agency’s Committee for Medicinal Products for Human Use granted accelerated assessment for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.

About the Collaboration between Daiichi Sankyo and AstraZeneca
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU (a HER2 directed ADC) in March 2019, and DS-1062 (a TROP2 directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and DS-1062.

U.S. FDA-Approved Indication for ENHERTU
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

SOURCE: Daiichi Sankyo

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